Cronkhite-Canada syndrome with colon cancer, portal thrombosis, high titer of antinuclear antibodies, and membranous glomerulonephritis

A 64-year-old man, who came to us with diarrhea, presented with ectodermal changes such as hyperpigmentation, alopecia, and onychatrophy, and was affected by polyposis in the colorectum and stomach. The polyps were histologically consistent with those in Cronkhite-Canada syndrome (CCS). Interestingly, the patient also had colon cancer, as well as portal thrombosis and a high concentration of antinuclear antibody. Treatment with prednisolone ameliorated the symptoms and the gastrointestinal polyposis, while the cancer was successfully treated with a hemicolectomy. Six months after the surgery, the patient developed nephropathy, with nephrotic-range proteinuria, without recurrence of the cancer. The biopsied renal specimen showed membranous glomerulonephritis. This is a rare case of CCS associated with various complications such as colon cancer, portal vein thrombosis, a high titer of antinuclear antibodies, and membranous glomerulonephritis. Although the pathogenesis of CCS is essentially unknown, these complications might have been indicative of an underlying immunological abnormality.     

Three cases of non-specific interstitial pneumonia associated with primary lung cancer

NSIP associated with primary lung cancer has been rarely reported. In the present report, three cases of histologically proven non-specific interstitial pneumonia (NSIP) associated with primary lung cancer are described. Importantly, in our 3 cases, interstitial pneumonia which is histologically proven to be NSIP was observed diffusely in both lungs. NSIP in these 3 cases responded to steroid therapy. However, 2 patients died from primary lung cancer and 1 patient died from progression of the interstitial pneumonia. Although the association between lung cancer and NSIP has been rarely documented, this combination was considered to be one of the paraneoplastic phenomena. The possible association between primary lung cancer and NSIP is discussed.     

Blood supply of the sinus node artery in beagle dogs

Summary Postmortem coronary angiography was performed in 20 beagles and 15 mongrels, and the origin and distribution of the sinus node arteries (SNAs) were subsequently investigated using soft X-ray radiography, the tissue clearing method, and histological examination. In 19 of 20 beagles, the SNAs consisted of a single atrial branch originating from the right coronary artery, and the distribution pattern of the atrial branch seemed to be uniform. In contrast, the following three different patterns were recognized in the atrial branches forming the SNAs of mongrels: (1) distribution by two atrial branches, i.e., one originating from the right coronary artery and the other from the left circumflex artery, (2) dual distribution by two atrial branches originating from the right coronary artery, and (3) distribution by a single atrial branch originating from the right coronary artery or from the left circumflex artery. In 26 of the 30 dogs which were histologically examined, the SNAs ran outside of the sinus node and were not centrally located. In the beagles, the proximal atrial branch from the right coronary artery reached the atrioventricuolar node area and supplied blood to the atrioventricular node together with the arterial branches derived from the anterior septal artery and posterior septal artery. In addition, the arterial branch of the SNAs reached the atrioventricular junction area. These findings should contribute to clinical, pharmacological, and pathological studies of the cardiovascular system, including studies on cardiac arrhythmias in beagles.     

Changes in serum levels of metalloproteinases and their inhibitors by treatment of chronic hepatitis C with interferon

We treated 18 patients with chronic hepatitis C by recombinant interferon-α (6 MIU for 24 weeks). In seven patients, serum aminotransferase levels declined to normal (responders). To evaluate the effect of interferon on matrix metalloproteinases (MMPs) and their inhibitors, namely tissue inhibitors of metalloproteinases (TIMPs), the serum levels of these enzymes were determined by enzyme immunoassay (EIA) using a specific monoclonal antibody. In responders, there was a tendency, but not a significant one, towards either an increase in serum MMP 1 levels or a decrease in serum TIMP 1 levels. In contrast, in nonresponders, both a significant decrease in MMP 1 and MMP 3 and a significant increase in TIMP 1 were observed. The number of cases of either increase in serum MMP levels or decrease in serum TIMP levels was significantly larger in responders than in nonresponders. Furthermore, the ratio of MMP 1 to TIMP 1 significantly increased in responders, suggesting that the balance between matrix formation and degradation in hepatic fibrosis tended to move toward degradation. These data indicate that interferon may exert a beneficial effect on hepatic fibrosis in parallel with improvement of aminotransferase activity.     

Usefulness of Streptococcus pneumoniae urinary antigen detection kit and the duration and intensity of reactivity with urinary antigen in patients with pneumonia]

We evaluated a rapid urinary antigen detection kit, Binax Now Streptococcus pneumoniae (Binax Inc., USA), which detects S. pneumoniae antigen in urine by immunochromatographic membrane assay, in 379 patients with presumptive pneumonia (total: 454 urine samples). S. pneumoniae antigen was detected in 64 (34%) of 188 patients. In all 64, pneumonia was diagnosed clinically, and there were 11 intense reactivity cases, 27 intermediate cases, and 26 weak cases. We found only two patients with positive sputum cultures for S. pneumoniae among 26 patients with weak reactivity to urinary antigen. The weak urinary antigen reactivity seems to include a false-positive result for S. pneumoniae pneumonia. There were five patients with negative results in whom S. pneumoniae was isolated (false-negative). We took intense and intermediate reactivity to be positive in order to diagnose pneumococcal pneumonia, and the kit showed a sensitivity of 72% and a specificity of 94% in 379 patients. The urinary antigen kit allowed us to diagnose 80% more patients with pneumococcal pneumonia than the use of conventional bacteriological diagnosis alone. There was no significant difference in the initial clinical characteristics, or in the severity of pneumonia among the three groups, according to the color intensity reached using the kit--weak, intermediate, and intense for the reactivity of urinary antigen. The duration of reactivity with S. pneumoniae urinary antigen did not correlate with the clinical characteristics or the severity of pneumonia. We concluded that S. pneumoniae urinary antigen detection kit is a useful adjunct to culturing for determining the etiology of pneumonia.     

Gore-Tex jump graft for portal vein thrombosis following living donor liver transplantation

Portal vein thrombosis is a rare surgical complication following liver transplantation, which remains a cause of graft loss and death. We describe here the treatment of portal vein thrombosis following living donor liver transplantation using an extended left lobe graft. The patient was treated with a Gore-Tex vascular jump graft extra-anatomically interposed between the recipient superior mesenteric vein and the donor umbilical vein. This technique allowed the hepatic hilum to be left untouched and supplied suitable blood flow to the hepatic allograft. Our experience suggests that this innovative technical solution can be helpful in the effort to rescue cases of hepatic allograft with vascular complications.     

Abnormal factor VIII Hiroshima: defect in crucial proteolytic cleavage by thrombin at Arg1689 detected by a novel ELISA

We have established an ELISA for detecting thrombin cleavage of the FVIII light chain at Arg¹⁶⁸⁹. The method used a coating alloantibody which recognized amino acid residues 2248–2312 in the C2 domain, together with a second monoclonal antibody, NMC-VIII/10, which recognized residues 1675–1684 in the amino-terminal region of the light chain. FVIII antigen (FVIII:Ag) was measured after treatment of plasma with various concentrations of thrombin. The FVIII:Ag of normal plasma was reduced in a dose-dependent manner by the thrombin, falling to 28% in the presence of 100 U/ml enzyme. The concentration of thrombin that achieved 50% reduction (IC₅₀) was approximately 1·0 U/ml. The plasma of four haemophilia A positive (A⁺) and two haemophilia A reduced (A^R) patients were analysed. The IC₅₀ of all patients was more than 1·0 U/ml, indicating that thrombin cleavage of the FVIII light chain was defective. One haemophilia A⁺ plasma did not respond to thrombin in this ELISA system. The patient (TI) was a haemophiliac with FVIII coagulant activity of 0·04 U/ml and FVIII:Ag of 1·78 U/ml. In addition, immunoblotting of the purified FVIII from TI showed that thrombin cleavage of the 80 kilodalton (kD) light chain was impaired. The patient's DNA was amplified using the polymerase chain reaction with a set of synthetic oligonucleotide primers spanning amino acid residues 1646–1714. Sequence analysis of the amplified DNA fragments revealed a cytosine to thymine transition, converting an arginine 1689 to cysteine. This abnormal FVIII was designated as FVIII Hiroshima. Our ELISA system is a simple and useful method of evaluating the proteolytic cleavage by thrombin at Arg¹⁶⁸⁹.     

Aggressive surgical resection for hepatocellular carcinoma with tumor thrombus extending to inferior vena cava and synchronous pulmonary metastasis

We describe a 66-year-old man having hepatocellular carcinoma with tumor thrombus extending into the inferior vena cava and synchronous pulmonary metastasis. He was referred to Chiba University Hospital on May, 2000, complaining of emaciation. Radiological findings showed a huge hepatocellular carcinoma in the entire right lobe and tumor thrombus extended into the intrapericardial inferior vena cava. He also had a solitary pulmonary metastasis in the left pulmonary lobe (stage IVB). Right hemihepatomy was performed under total hepatic vascular exclusion without cardiopulmonary bypass, and tumor thrombus was completely removed. Thoracoscopic wedge resection of pulmonary metastasis was also performed. The patient had an uneventful postoperative course. Histopathological examination revealed that the tumor was moderately differentiated hepatocellular carcinoma The patient is still alive after 26 months with pulmonary recurrence, but without hepatic recurrence. To our knowledge, there has been no reported case of resection for both hepatocellular carcinoma invading the inferior vena cava and synchronous pulmonary metastasis. In conclusion, aggressive surgical resection for advanced hepatocellular carcinoma concomitant with pulmonary resection may bring about better prognosis in highly selected patients.     

Morphology and biochemistry of the lung from guinea pig after repeated injections of freund’s complete adjuvant

Guinea pigs received 5 daily injections of Freund’s complete adjuvant and the changes in the lung were investigated by light microscope and electron microscope. In the 20th week of experiment, fibrotic changes were found around the granulomata close to the surface of the lung. In addition the fraction of glycosaminoglycans was isolated from the lung and analyzed quantitatively. As a result, a decrease in quantity of hyaluronic acid and an increase in quantity of dermatan sulfate were observed.     

Age- and sex-dependent DNA hypomethylation controlled by growth hormone in mouse liver

In mammals, differences in liver function and aging have been observed between sexes; however, the epigenetic mechanisms underlying such differences remain largely unexplored. In this study, we investigated sex- and age-dependent DNA methylation status in the mouse liver. We analyzed 90 known sex-differentially expressed genes, and identified sex-dependent methylation in Zfp809, Hsd3b5, Treh, Cxcl11, Cyp17a1, and Nnmt genes. After 4 weeks of age, we noted the gradual establishment of sex-dependent hypomethylation in each of these genes in either males or females. The exposure of male mice to female-like growth hormone (GH) profile repressed male-predominant hypomethylation and promoted female-predominant hypomethylation. The occurrence of age-dependent hypomethylation, including at loci for which we also observed sex-dependent changes in DNA methylation, was accompanied by the downregulation of DNMT3A/B. In addition, we found that age-dependent hypomethylation was promoted through liver regeneration induced by partial hepatectomy, suggesting that DNMT activities were not enough to retain methylation levels. In conclusion, our results demonstrate that sex-dependent GH profiles influence the age-progressive hypomethylation under decreased DNMT3A/B levels in certain regions of the genome.